A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa
TEMPRANO ANRS 12136 Study Group, Christine Danel, Raoul Moh, Delphine Gabillard, Anani Badje, Jérôme Le Carrou, Timothée Ouassa, Eric Ouattara, Amani Anzian, Jean-Baptiste Ntakpé, Albert Minga, Gérard M Kouame, Franck Bouhoussou, Arlette Emieme, Antoine Kouamé, André Inwoley, Thomas-d'Aquin Toni, Hugues Ahiboh, Mathieu Kabran, Cyprien Rabe, Baba Sidibé, Gustave Nzunetu, Romuald Konan, Joachim Gnokoro, Patrice Gouesse, Eugène Messou, Lambert Dohoun, Synali Kamagate, Abo Yao, Solange Amon, Amadou-Barenson Kouame, Aboli Koua, Emmanuel Kouamé, Yao Ndri, Olivier Ba-Gomis, Marcelle Daligou, Simplice Ackoundzé, Denise Hawerlander, Alex Ani, Fassery Dembélé, Fatoumata Koné, Calixte Guéhi, Constance Kanga, Serge Koule, Jonas Séri, Mykayila Oyebi, Nathalie Mbakop, Olewole Makaila, Carole Babatunde, Nathanael Babatounde, Gisèle Bleoué, Mireille Tchoutedjem, Alain-Claude Kouadio, Ghislaine Sena, Sahinou-Yediga Yededji, Rodrigue Assi, Alima Bakayoko, Alassane Mahassadi, Alain Attia, Armel Oussou, Max Mobio, Doféré Bamba, Mesmin Koman, Apollinaire Horo, Nina Deschamps, Henri Chenal, Madeleine Sassan-Morokro, Seidou Konate, Kakou Aka, Eba Aoussi, Valérie Journot, Célestin Nchot, Sophie Karcher, Marie-Laure Chaix, Christine Rouzioux, Papa-Salif Sow, Christian Perronne, Pierre-Marie Girard, Hervé Menan, Emmanuel Bissagnene, Auguste Kadio, Virginie Ettiegne-Traore, Corinne Moh-Semdé, Abo Kouame, Jean-Marie Massumbuko, Geneviève Chêne, Mireille Dosso, Serge K Domoua, Thérèse N'Dri-Yoman, Roger Salamon, Serge P Eholié, Xavier Anglaret, Kakou Aka, Eba Aoussi, Emmanuel Bissagnene, Serge Eholie, Auguste Kadio, Gustave Nzunetu, Cyprien Rabe, Baba Sidibé, Amani Anzian, Joachim Gnokoro, Patrice Gouesse, Eugène Messou, Lambert Dohoun, Synali Kamagate, Seidou Konate, Albert Minga, Yao Abo, Solange Amon, Kouame Barenson Amadou, Aboli Koua, Emmanuel Kouamé, Ben-Ahoussi Ndja, Yao Ndri, Simplice Ackoundzé, Olivier Ba-Gomis, Henri Chenal, Marcelle Daligou, Denise Hawerlander, Alex Ani, Fassery Dembélé, Calixte Guéhi, Constance Kanga, Fatoumata Kone, Serge Koule, Jonas Séri, Blandine Adou, Oyebi Mykayila, Nathalie Mbakop, Olewole Makaila, Yves-Alain Zike, Claude Akakpo, Carole Babatunde, Nathanael Babatounde, Gisèle Bleoue, Mireille Tchoutedjem, Madeleine Sassan-Morokro, Alain-Claude Kouadio, Ghislaine Sena, Sahinou Yediga Yededji, Rodrigue Assi, Alima Bakayoko, Serge K Domoua, Max Mobio, Bamba Doféré, Koman Mesmin, Alain Attia, Alassane Mahassadi, Therèse Ndri-Yoman, Apollinaire Horo, Armel Oussou, Hugues Ahiboh, Arlette Emieme, André Inwole, Mathieu Kabran, Hervé Menan, Timothée Ouassa, Thomas-d'Aquin Toni, Christine Rouzioux, Marie-Laure Chaix, Gilles Peytavin, Mariatou Koné, Kouamé N'Guessan, Raïmi Fassassi, Serge Niangoran, Frédéric Lemarcis, Charlotte Brives, Annabel Desgrées-du-Loû, France Lert, Rosemary Dray Spira, Kevin Jean, Christine Danel, Raoul Moh, Romuald Konan, Anani Badjé, Jean-Baptiste Ntakpé, Gérard Menan Kouamé, Franck Bohoussou, Cyril Yao-Yapi, Larissa N'guessan Koffi, Bertine Siloué, Adoulaye Cissé, Adrienne Aboua, Sylvie Konan, Antoine Kouamé, Celestin N'Chot, Elvis Amani, Thérèse Ndri-Yoman, Xavier Anglaret, Delphine Gabillard, Valérie Journot, Jérôme Le Carrou, Eric Ouattara, Sophie Karcher, Gwenaëlle Clouet, Bruno Debono, Emmanuel Bissagnene, Geneviève Chêne, Serge K Domoua, Mireille Dosso, Pierre-Marie Girard, Vincent Jarlier, Jean-Marie Massumbuko, Christian Perronne, Papa-Salif Sow, TEMPRANO ANRS 12136 Study Group, Christine Danel, Raoul Moh, Delphine Gabillard, Anani Badje, Jérôme Le Carrou, Timothée Ouassa, Eric Ouattara, Amani Anzian, Jean-Baptiste Ntakpé, Albert Minga, Gérard M Kouame, Franck Bouhoussou, Arlette Emieme, Antoine Kouamé, André Inwoley, Thomas-d'Aquin Toni, Hugues Ahiboh, Mathieu Kabran, Cyprien Rabe, Baba Sidibé, Gustave Nzunetu, Romuald Konan, Joachim Gnokoro, Patrice Gouesse, Eugène Messou, Lambert Dohoun, Synali Kamagate, Abo Yao, Solange Amon, Amadou-Barenson Kouame, Aboli Koua, Emmanuel Kouamé, Yao Ndri, Olivier Ba-Gomis, Marcelle Daligou, Simplice Ackoundzé, Denise Hawerlander, Alex Ani, Fassery Dembélé, Fatoumata Koné, Calixte Guéhi, Constance Kanga, Serge Koule, Jonas Séri, Mykayila Oyebi, Nathalie Mbakop, Olewole Makaila, Carole Babatunde, Nathanael Babatounde, Gisèle Bleoué, Mireille Tchoutedjem, Alain-Claude Kouadio, Ghislaine Sena, Sahinou-Yediga Yededji, Rodrigue Assi, Alima Bakayoko, Alassane Mahassadi, Alain Attia, Armel Oussou, Max Mobio, Doféré Bamba, Mesmin Koman, Apollinaire Horo, Nina Deschamps, Henri Chenal, Madeleine Sassan-Morokro, Seidou Konate, Kakou Aka, Eba Aoussi, Valérie Journot, Célestin Nchot, Sophie Karcher, Marie-Laure Chaix, Christine Rouzioux, Papa-Salif Sow, Christian Perronne, Pierre-Marie Girard, Hervé Menan, Emmanuel Bissagnene, Auguste Kadio, Virginie Ettiegne-Traore, Corinne Moh-Semdé, Abo Kouame, Jean-Marie Massumbuko, Geneviève Chêne, Mireille Dosso, Serge K Domoua, Thérèse N'Dri-Yoman, Roger Salamon, Serge P Eholié, Xavier Anglaret, Kakou Aka, Eba Aoussi, Emmanuel Bissagnene, Serge Eholie, Auguste Kadio, Gustave Nzunetu, Cyprien Rabe, Baba Sidibé, Amani Anzian, Joachim Gnokoro, Patrice Gouesse, Eugène Messou, Lambert Dohoun, Synali Kamagate, Seidou Konate, Albert Minga, Yao Abo, Solange Amon, Kouame Barenson Amadou, Aboli Koua, Emmanuel Kouamé, Ben-Ahoussi Ndja, Yao Ndri, Simplice Ackoundzé, Olivier Ba-Gomis, Henri Chenal, Marcelle Daligou, Denise Hawerlander, Alex Ani, Fassery Dembélé, Calixte Guéhi, Constance Kanga, Fatoumata Kone, Serge Koule, Jonas Séri, Blandine Adou, Oyebi Mykayila, Nathalie Mbakop, Olewole Makaila, Yves-Alain Zike, Claude Akakpo, Carole Babatunde, Nathanael Babatounde, Gisèle Bleoue, Mireille Tchoutedjem, Madeleine Sassan-Morokro, Alain-Claude Kouadio, Ghislaine Sena, Sahinou Yediga Yededji, Rodrigue Assi, Alima Bakayoko, Serge K Domoua, Max Mobio, Bamba Doféré, Koman Mesmin, Alain Attia, Alassane Mahassadi, Therèse Ndri-Yoman, Apollinaire Horo, Armel Oussou, Hugues Ahiboh, Arlette Emieme, André Inwole, Mathieu Kabran, Hervé Menan, Timothée Ouassa, Thomas-d'Aquin Toni, Christine Rouzioux, Marie-Laure Chaix, Gilles Peytavin, Mariatou Koné, Kouamé N'Guessan, Raïmi Fassassi, Serge Niangoran, Frédéric Lemarcis, Charlotte Brives, Annabel Desgrées-du-Loû, France Lert, Rosemary Dray Spira, Kevin Jean, Christine Danel, Raoul Moh, Romuald Konan, Anani Badjé, Jean-Baptiste Ntakpé, Gérard Menan Kouamé, Franck Bohoussou, Cyril Yao-Yapi, Larissa N'guessan Koffi, Bertine Siloué, Adoulaye Cissé, Adrienne Aboua, Sylvie Konan, Antoine Kouamé, Celestin N'Chot, Elvis Amani, Thérèse Ndri-Yoman, Xavier Anglaret, Delphine Gabillard, Valérie Journot, Jérôme Le Carrou, Eric Ouattara, Sophie Karcher, Gwenaëlle Clouet, Bruno Debono, Emmanuel Bissagnene, Geneviève Chêne, Serge K Domoua, Mireille Dosso, Pierre-Marie Girard, Vincent Jarlier, Jean-Marie Massumbuko, Christian Perronne, Papa-Salif Sow
Abstract
Background: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast.
Methods: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies.
Results: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies.
Conclusions: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).
Source: PubMed